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Postencephalitic parkinsonism

Neurofibrillary tangles (NFT) are found in several neurodegenerative disorders including Alzheimer's disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), amyotrophic lateral sclerosis/ parkinsonism-dementia complex of Guam (ALS/PDC) and to a lesser extent Pick's disease (PiD). In AD, NFT result from the intraneuronal aggregation of pathological tau proteins, composed of a characteristic triplet made of tau 60, 64, and 69, also referred to as tau-PHF or A68. Pathological tau proteins are more extensively phosphorylated than tau proteins found in biopsy-derived materials and show a more acidic isoelectric point.

In Guamanian ALS/PDC, this tau triplet is also observed. However, PSP and CBD display a typical tau doublet made of tau 64 and 69 (Flament et al., 1991; Buee-Scherrer et al., 1996), whereas in PiD cases, a characteristic tau doublet composed only of tau 60 and 64 is observed (Buee-Scherrer et al., 1996; Delacourte et al., 1996).

Some patients who survived the influenza pandemic in the years 1916-1926 later developed postencephalitic parkinsonism (PEP). These patients do not exhibit any cognitive changes and are usually neither aphasic nor apraxic.

The immunohistochemical analysis of the PEP cases demonstrated that NFT are found in variable densities in the hippocampus and entorhinal cortex, areas 4, 9 and 20 and in subcortical regions. Higher NFT densities are observed in the hippocampal formation and area 20, compared to areas 4 and 9, and the putamen, indicating that some regions are preferentially affected by the degenerative process. In addition, NFT are more numerous in supragranular than in the infragranular layers (Hof et al., 1992) contrasting with AD cases, but similar to other disorders such as ALS/PDC of Guam, CBD, PSP...

The PEP cases display the tau 60, 64 and 69 triplet in cortical and subcortical brain regions in contrast to AD cases where this triplet is mainly restricted to the hippocampal formation and association neocortex. Also, the tau triplet is found in brain areas usually spared in AD including primary motor cortex and basal ganglia. The regional distribution of the tau triplet differs among PEP cases, suggesting some heterogeneity in the neurodegenerative process.

It is interesting to note that in ALS/PDC of Guam, the cases exhibit the same electrophoretic tau profile (Buée-Scherrer et al., Ann Neurol, 41 (1997)). Thus, environmental toxins (ALS/PDC of Guam) and viruses (PEP ; exposition to the pandemic of influenza) may lead to a similar neuropathology.


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